MPV-2426 [4-(6-hydroxyindan-1-ylmethyl)-1H-imidazol-1-ium chloride] is disclosed in U.S. Pat. No. 6,313,311 B1 as an alpha2 agonist useful in the treatment of hypertension, glaucoma, migraine, diarrhea, ischemia, addiction to chemical substances, anxiety, e.g. preoperative anxiety, and different neurological, musculoskeletal, psychiatric and cognition disorders as well as a sedative and an analgesic agent, nasal decongestant, and as an adjunct to anaesthesia. MPV-2426 provides a spatially restricted and effective antinociception with minor side effects. Intraspinal, intrathecal or epidural administration of MPV-2426 is disclosed in WO 00/18400 A1. The treatment of hypotension, shock, and cardiopulmonary resuscitation by administering MPV-2426 is disclosed in WO 01/30347 A1.
Alpha2 agonists are known to decrease intraocular pressure (IOP). The first report of the IOP lowering effects of these therapeutic agents was published in 1966 [Makabe, R. Dtsch. Med. Wochenschr., 91 (1966) 1686].
Prodrugs are pharmacologically inactive derivatives of drug molecules that after chemical or enzymatic transformation release the active drug exerting the therapeutic action. Prodrugs are designed to overcome various pharmaceutical or biopharmaceutical problems associated with the parent drug. A prodrug with good permeation across biological membranes should exhibit optimum lipophilicity. In addition, a prodrug should be stable enough against chemical degradation and revert to the active parent drug via enzymatic hydrolysis in the body during or after absorption.